1
Summary
of
Summary
of
EPA
Ethics
Review
EPA
Ethics
Review
Nethercott,
J.,
Paustenbach,
D.,
Adams,
R,
et
al.(
1994)
A
study
of
chromium
induced
allergic
contact
dermatitis
with
54
volunteers:
implications
for
environmental
risk
assessment.
Occup.
Environ
Med
1994;
51:
371­
380.
(
MRID
46803602)
2
Cr
Cr­
VI
ACD
Study
VI
ACD
Study

Study
in
Chrome­
sensitized
subjects

Conducted
by
6
dermatologists

Designed
to
resolve
uncertainties
resulting
from
prior
work

Minimal
reporting
of
ethical
conduct
3
Cr
Cr­
VI
VI
"
Framework
Framework"

1.
Value

Undertaken
to
resolve
questions
raised
by
inconsistencies
among
earlier
studies

Results
were
published,
to
the
benefit
of
society
2.
Scientific
Validity:
Defer
to
others
4
Cr
Cr­
VI
VI
"
Framework
Framework"
­­

­­
2
3.
Subject
Selection

6000
patient
files
screened

102
adult
male
and
female
volunteers
participated
in
first
phase

54
subjects
confirmed
to
be
Cr­
sensitized
participated
in
later
phases

Standards
for
inclusion
or
exclusion
were
based
on
the
scientific
goals
of
the
study

Use
of
investigators'
patients
introduces
role
ambiguity;
not
addressed
5
Cr
Cr­
VI
VI
"
Framework
Framework"
­­

­­
3
4.
Risk­
Benefit
Ratio

Societal
benefit
of
knowledge
expected
not
addressed

Many
subjects
benefited
directly
by
learning
they
were
not
Cr­
sensitized.

5.
Independent
Ethics
Review

Approved
by
investigators'
"
respective
human
use
committees
as
appropriate"


No
further
documentation
6
Cr
Cr­
VI
VI
"
Framework
Framework"
­­

­­
4
6.
Informed
Consent

Written
consent
from
all
subjects
asserted

No
documentation
of
consent
materials

Silent
about
further
consent
for
special
tests
7.
Respect
for
Subjects

Subject
privacy
was
not
compromised

Subject
freedom
to
withdraw
not
reported
(
11
potential
subjects
withdrew
 
for
personal
reasons 
before
testing)
7
Cr
Cr­
VI
Prevailing
Standards
VI
Prevailing
Standards

Conducted
in
the
U.
S.
and
Canada
in
1992

No
standard
of
conduct
cited
in
report

Dermatologists
likely
to
be
familiar
with
HEW
rules
at
45
CFR
46

Declaration
of
Helsinki
(
1989)
also
assumed
to
apply
8
Comparison
to
Comparison
to
DoH
DoH

Basic
Principle
#
2:
".
.
.
Each
experimental
procedure
.
.
should
be
clearly
formulated
in
an
experimental
protocol,
which
should
be
transmitted
.
.
to
a
specially
appointed
committee
.
.
."


EPA
Comment:
No
protocol
available.

Reviewing
ethics
committees
incompletely
identified;
ethics
reviews
undocumented
9
Comparison
to
Comparison
to
DoH
DoH
­­

­­
2

Basic
Principle
#
5:
"
Every
.
.
.
project
.
.
.

should
be
preceded
by
careful
assessment
of
predictable
risks
in
comparison
with
foreseeable
benefits
to
the
subject
or
to
others."


EPA
Comment:
If
a
careful
assessment
was
conducted
it
was
not
reported
10
Comparison
to
Comparison
to
DoH
DoH
­­

­­
3

Basic
Principle
#
9:
"
each
potential
subject
must
be
adequately
informed
of
the
aims,

methods,
anticipated
benefits
and
potential
hazards
of
the
study
and
the
discomfort
it
may
entail.
.
."


EPA
Comment:
The
study
reports
obtaining
consent,
but
does
not
report
what
subjects
were
told
11
Comparison
to
Comparison
to
DoH
DoH
­­

­­
4

Basic
Principle
#
10:
"
When
obtaining
informed
consent
for
the
research
project
the
physician
should
be
particularly
cautious
if
the
subject
is
in
a
dependent
relationship
to
him.
."


EPA
Comment:
Subjects
were
all
former
patients
of
the
investigators.
Role
shift
from
doctor/
patient
to
investigator/
subject
was
not
acknowledged
or
addressed
12
Comparison
to
Comparison
to
DoH
DoH
­­

­­
5

Basic
Principle
#
12:
"
The
research
protocol
should
always
contain
a
statement
of
the
ethical
considerations
involved
.
.
.
."


EPA
Comment:
The
report
is
silent
about
ethical
considerations
13
Comparison
to
45
CFR
46
Comparison
to
45
CFR
46

§
46.109(
b):
"
An
IRB
shall
require
that
information
given
to
subjects
as
part
of
informed
consent
is
in
accordance
with
§
46.116."


EPA
Comment:
The
study
does
not
report
what
subjects
were
told
as
part
of
informed
consent
14
Comparison
to
45
CFR
46
Comparison
to
45
CFR
46

§
46.111:
Criteria
for
IRB
approval

EPA
Comment:
There
is
no
record
of
IRB
determinations
that
all
criteria
in
§
46.111
were
satisfied
§
46.116:
General
requirements
for
Informed
Consent

EPA
Comment:
Can't
tell
if
they
were
met
15
Chrome
Chrome­
VI
Summary
VI
Summary

Gaps
in
the
record,
but
gaps
are
not
"
clear
and
convincing
evidence"


No
evidence
that
the
research
was
fundamentally
unethical

No
evidence
that
subjects
included
children
or
pregnant
women

Some
possible
deficiencies
relative
to
prevailing
ethical
standards

We
welcome
the
Board's
advice
on
the
significance
of
those
deficiencies
